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Biomarker Indicates Suitability of Stroke Therapy

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Scientists have identified a blood protein biomarker they claim can more accurately determine the time of an ischemic stroke onset than current approaches, and potentially increase five-fold the number of patients eligible for thrombolytic rt-PA (recombinant tissue plasminogen activator) therapy. The protein, GST-n, was identified by researchers at the University of Geneva (UNIGE) working in collaboration with colleagues at Proteome Sciences, through a long-term prospective study that measured levels of 29 proteins in the blood of hundreds of stroke patients and controls. The 29 proteins had previously been identified by Proteome Sciences as early markers of brain damage associated with stroke.

Of these, blood levels of GST-n were found to increase rapidly after the onset of stroke, peaking at three hours and returning to normal by six hours, and providing an indication of whether or not a patient will benefit from thrombolytic therapy. The study is reported in PLoS One in a paper titled “Blood Glutathione S-Transferase-π as a Time Indicator of Stroke Onset.”

By the time a patient reaches hospital with symptoms of an ischemic stroke it can be very hard to determine when that stroke actually began. Patients for whom this time-frame can’t be determined won’t receive rt-PA, which needs to be given within the first 3–4 hours of stroke onset if it is to be effective.

To try and identify a blood biomarker that can provide this predictor, the UNIGE researchers carried out a study to measure levels of 29 proteins on a prospective cohort of 103 stroke victims admitted to the Geneva University Hospital, and another 132 controls. All the patients had been admitted within 72 hours of symptom onset. The results of blood tests from these patients were then compared with those from patients in an independent cohort of acute ischemic stroke patients admitted to a Spanish hospital within the first three hours of stroke onset.

The results showed that GST-n was the most significantly elevated marker in the blood of stroke patients within the first few hours of onset, and even more importantly, demonstrated the best area under the curve and the best diagnostic odds ratios for discriminating early and late stroke patients. In fact, blood levels of the protein accurately predicted the time of stroke onset in over 50% of early stroke patients.

The findings represent a major step toward improving the management of ischemic stroke patients using currently available drugs, claims Jean-Charles Sanchez, Ph.D., who led the study in Geneva. “A simple blood test that matches the therapeutic window of rt-PA is a major advance that we encourage clinicians, pharmaceutical, and diagnostics companies to unite to rapidly bring this into routine practice to improve patient outcomes.”

Proteome Sciences inked a deal with Randox Laboratories in April through which the latter has a license to use Proteome’s plasma biomarkers in the development of products for the early diagnosis of stroke and subsequent monitoring of treatment outcomes. “We expect to complete additional licenses with both diagnostic and pharmaceutical companies to ensure the technology is developed as quickly as possible to be used as a diagnostic tool for the use of rt-PA as a treatment,” states Ian Pike, M.D., Proteome’s COO.

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